Objective Acute myocardial infarction (AMI) and subsequent myocardial ischemia-reperfusion injury (MIRI) pose major clinical challenges. Understanding MIRI's molecular mechanisms is crucial for developing effective therapies. This study aims to elucidate the role of Dehydrogenase/Reductase 7C (DHRS7c) in MIRI, investigate its upstream regulatory factors, and study the interactions among these genes. Method H9c2 cardiac cells were exposed to hypoxia/reoxygenation (H/R) conditions to mimic the intracellular changes that occur in the setting of MIRI. DHRS7c, Spi-1 Proto-oncogene (SPI1), and DNA methyltransferase 1 (DNMT1) were amplified or inhibited to study their roles. The effects of these treatments on H9c2 cells at multiple levels (quantitative reverse transcription-polymerase chain reaction, western blot analysis and Cell Counting Kit-8) was examined among different conditions. The interaction between SPI1 and DHRS7c was assessed using a dual-luciferase reporter system, and the regulation of DHRS7c by histone modification and methylation was investigated. Examine oxidative stress-related markers, iron levels, and mitochondrial damage after ferroptosis occurs on cells that have been stimulated by H/R exposure. Result DHRS7c overexpression promotes cell survival and decreases the degree of oxidation and ferroptosis to protect cells from injury caused by H/R. DHRS7c knockdown significantly increased the sensitivity to injury. SPI1 depletion inhibited DHRS7c expression, promoted H/R injury; DNMT1 knockdown reversed the effects of SPI1 knockdown and improved cell viability. Conclusion DHRS7c protects H9c2 cells against H/R injury, and that this effect is mediated through SPI1 regulation and DNMT1-dependent methylation. These findings provide possible therapeutic targets for MIRI treatment.
Hu et al. (Fri,) studied this question.